PB2215: HYDROXYUREA-INDUCED CUTANEUS ADVERSE EVENTS IN PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA: A SINGLE-CENTER EXPERIENCE
Authors: Amaia Lopez Peña, Marta Sofia Ordas Miguelez, Carmen Rodriguez Lefler, Jhossyuriel Obregon Membreño, Rita Gonzalez Resina, Laura Fernandez Cuezva, Mar Herrero Gutierrez, Pablo Estuardo Lopez Gomez, Leire Etxebarria Bahillo, Laura Villarroya Martínez, Rafael Monleon Gil, Pilar Delgado Beltran, Gonzalo Caballero Navarro
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Hydroxyurea (HU) is an S-phase specific oral chemotherapeutic agent that causes cell death by inhibiting the ribonucleotide diphosphate reductase. It is the most common used cytoreductive drug in BCR-ABL1 negative myeloproliferative neoplasms. Although HU is well tolerated, cytopenias and cutaneous adverse events, such us ulcers, oral aphthae, nail disorders, actinic keratoses and neoplasms are frequent and can limit its long-term use. HU is not recommended neither in patients with personal history of ulcers nor in those who present them during treatment. Aims: To describe and analyze the cutaneous toxicity caused by HU in patients with essential thrombocythemia (ET) and its evolution. Methods: Observational, descriptive and retrospective study based on patients diagnosed with ET that were included in the Spanish ET Registry (RETE) between November 1995 and May 2021 from our center. A sample of patients with HU-induced skin toxicity was selected. Demographic, anthropometric and clinical variables, mucocutaneous history and therapeutic aspects were analyzed. Results: 115 patients were diagnosed with ET and 94 received treatment with HU. Of the latter, skin toxicity was detected in 13 patients, representing 13.8% of patients and constituting our sample. Seven out of thirteen (53.8%) were women and the median age at diagnosis was 68 years (56-75). None of the patients had history of dermatological diseases. Eight out of thirteen (61.5%) had CALR mutations (type 1, type 2, 30 bp-deletion or c.1100_1145del), four (30.8%) JAK2 V617F mutation and one (7.7%) was triple-negative. None carried MPL mutations. The majority of patients (9/13) presented leg ulcers, mainly in lateral malleolus. Eczematous reaction was observed in two patients and dermatitis and palmar dyshidrosis in one case. Likewise, one patient presented oral aphthae and ulcers and another one nail pigmentation. One had numerous actinic keratoses with subsequent evolution to squamous and basal cell carcinomas before HU discontinuation (Figure 1). Treatment time until the appearance of cutaneous lesions ranges from 1 to 97 months, with a median of 59 months (13.2-75). The doses needed for lesions to appear vary from 10.8 to 18.7 mg/Kg/day, with a median of 13.8 mg/Kg/day (13.2-14.4). After discontinuing HU, 11 patients (84.6%) achieved clinical improvement, requiring a median time of 1.7 months (1-8.1) until the lesions disappeared. The patient who progressed to skin cancer did not show improvement after removing HU, needing specific dermatological treatment. Anagrelide was used as second-line treatment in ten patients (76.9%), while one patient was treated with Ruxolitinib and another one with Melfalan, with good tolerance. One of the patients, despite presenting ulcers in multiple locations without improvement after discontinuation of HU, had to restart it due to comorbidity and contraindication to receive other lines. Four patients died during follow-up because of non-hematological causes. Summary/Conclusion: The main cause of HU discontinuation in our patients included in RETE was skin toxicity, with a median appearance of lesions of almost 5 years. This side effect may be underdiagnosed, requires a high rate of suspicion and has an impact on quality of life. Accordingly, close dermatological monitoring and early removal of HU is essential.Keywords: Hydroxyurea, Essential Thrombocytemia, Toxicity